The insulin receptor has been studied in a variety of animal species including mammals, birds, amphibians, bony fish and cyclostomes. In the North Atlantic hagfish both the insulin receptor and hagfish insulin have been studied. Despite nearly a half million years of divergent evolution, the insulin receptor in this primitive vertebrate maintained remarkably similar binding properties, including saturability, reversibility, specificity, temperature and pH dependence, as well as negative cooperativity. Hagfish insulin has 5-10% bioactivity and binding as that of pork insulin on mammalian tissues, and can induce negative cooperativity.